text: DX-9065a, the first small molecule direct Xa-inhibitor, is an amidinoaryl derivate with a molecular weight of 571.07g/mol. Its positively charged amidinonaphtalene group forms a salt bridge to the Asp-189 residue in the S1 pocket of FXa. The pyrrolidine ring fits between Tyr-99, Phe-174 and Trp-215 in the S4 pocket of FXa.
  Unlike older drugs, e.g. heparin, DX-9065a is selective for FXa compared to thrombin even though FXa and thrombin are similar in their structure. This is caused by a difference in the amino acid residue in the homologue position 192. While FXa has a glutamine residue in that position, thrombin has a glutamic acid that causes electrostatic repulsion with the carboxyl group of DX-9065a. In addition, a salt bridge between Glu-97 of thrombin and the amidine group fixed in the pyrrolidine ring of DX-9065a reduces the flexibility of the DX-9065a molecule, which now cannot rotate enough to avoid the electrostatic clash. That's why the IC value for thrombin is >1000µM while the IC value for FXa is 0,16µM.